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Professor researches potential allergy treatment

ABI HOVERMAN | Thursday, October 17, 2013

BasarBilgicer, assistant professor in the Department of Chemical and Biomolecular Engineering and Advanced Diagnostics and Therapeutics Initiative, said groundbreaking scientific advances have taken a step towards preventative treatment possible for millions of Americans who suffer from life-threatening allergies.

He said he and his team have made progress towards the first-ever inhibitory therapy for Type I Hypersensitive allergic reactions.

“These type of allergies are potentially lethal,” he said. “Unfortunately, there are no available medications that can prevent the occurrence of an allergic response to … Type I allergies.”

Type I hypersensitive responses occur by the components of the immune system designed to fight harmful parasites when mast cells and basophils, both of which are types of white blood cells, respond to harmless allergens with symptoms that can be as devastating as potentially lethal anaphylactic shock, Bilgicer said.

The only treatments currently available for severe allergies, like an EpiPen, attempt to manage symptoms until a victim can be taken to the hospital, Bilgicer said.

Bilgicer, also part of the Center for Rare and Neglected Diseases and the Harper Cancer Center, said his team of Notre Dame researchers are working on the design and synthesis of Heterobivalent Inhibitors (HBI), which bind more effectively to mast cells and basophils than allergens like shellfish and peanuts.

“Our approach is to stop it before it takes place,” Bilgicer said. “Our molecules are designed so that they will compete with the allergen molecule in binding to the receptor in mast cells and basophils. Our molecule binds more effectively, blocking binding of allergens and keeping allergic reactions from happening in the first place.”

He said HBI molecules have worked successfully in cellular and animal tests in mice, and although all the ideas were developed at Notre Dame, his group has been in collaboration with Dr. Mark Kaplan’s at Indiana University (IU).

“We did all the design and synthesis here,” Bilgicer said. “The animal studies were verified at IU Med School in Dr. Kaplan’s lab.”

This allergy research has been in development since Bilgicer joined the Notre Dame faculty in 2008, and he said Dr. Michael Handlogten, a recently graduated PhD student, worked as the leading scientist on the project since its initiation. Bilgicer said the most updated version of these advances, included the findings from the mice studies, were published in the Nature Chemical Biology Journal.

Bilgicer said Notre Dame partly funded his research, but the project also received support from the National Institute of Health’s National Institute of Allergic and Infections Diseases.

Society increasingly needs this groundbreaking inhibitory treatment, as Type I allergies become more prevalent, Bilgicer said.

“At present, there is a strong prevalence of peanut allergies, unfortunately,” he said. “The number of cases is increasing.”.

People could eventually use Bilgicer’sHPI research with severe allergies in multiple ways, he said. First, it could work to replace an EpiPen if symptoms of a reaction begin to occur. It could also be used if an exposure to a deadly allergen is likely, like when sending a child to school, he said.

“If you are allergic to peanuts and you know you are getting on a flight, you could take an HPI,” he said. “The dust from the guy next to you opening a bag of peanuts can cause deadly reactions, which has happened before.”

He said another important usage could be in Immunotherapy, which involves slow exposure to an allergen so that they body gradually learns that the allergen is not actually harmful, eventually leading to tolerance. Currently, he said most Type I allergy sufferers cannot safely be exposed to any amount of their allergen.

“We could give the allergen in presence of HPI to control the effects of the allergen and reduce the symptoms for a patient,” he said. “Therefore, HBI can potentially be used in conjunction with immunotherapy to treat Type I hypersensitivity.”

Bilgicer said he plans to develop a specific HPI for each type of allergen that causes Type I allergic reactions.

“The next step is to take this away from model system and into a system where it would be more relevant to natural allergens,” he said. “The HBI needs to be redesigned for every new allergen. To inhibit, say, peanuts we have to make a new HBI, and that is the next step in our research.”